Jpn. J. Pharmacol. 86 (4), 376-380 (2001)

REVIEW -Current Perspective-
Strategy for Modulation of Central Dopamine Transmission Based on the Partial Agonist Concept in Schizophrenia Therapy

Atsuko Inoue* and Yoshihiro Nakata

Department of Pharmacology, Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan

*Corresponding author. FAX: +81-82-257-5314, E-mail:

Abstract: The dopamine system is known to be closely involved in brain neuronal dysfunction and in diseases such as Parkinson's disease, Tourette's syndrome, attention deficit hyperactive disorder, generation of pituitary tumors and schizophrenia. According to the classical dopamine hypothesis on the pathology of schizophrenia, conventional antipsychotics has D2 dopamine receptor antagonistic profiles. However, the use of typical antipsychotics has several limitations; that is, some patients do not respond to them, they can even worsen negative symptoms, and they can provoke unacceptable extrapyramidal and endocrine side effects. To produce effective antipsychotics with reduced side effects, partial agonists to D2 dopamine receptors (D2 receptors) have been developed. Despite the effectiveness of partial agonists for pre- and post-synaptic D2 receptors, administration of such drugs results in inconsistent clinical effects to ameliorate the symptoms of schizophrenia. Thus, strategies for obtaining ideal effective antipsychotics with reduced side effects are considered in this short review with respect to the intrinsic efficacies and affinities of the partial agonists, based on the partial agonist concept.

Keywords: Dopamine receptor, Antipsychotic, Partial agonist, Intrinsic efficacy, Affinity, Schizophrenia
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